Animal models of preeclampsia: translational failings and why

Abstract

Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia. This review summarizes the various types and characteristics of animal models used to study preeclampsia, highlighting particular features of these models relevant to clinical translation. This review points out the strengths and limitations of these models to illustrate the importance of using the appropriate model depending on the research question.

Comparative Effects of Aqueous Leaf Extracts of Thymus schimperi and Moringa stenopetala on Regional Blood Flow Velocity and Vascular Resistance of Pre-eclampsia Rat Models

“…These findings are consistent with findings of PI in the growth-retarded fetuses where the PI was reduced in the internal carotid artery and raised in the descending aorta and umbilical arteries, suggesting an increased peripheral vascular resistance in the fetal body and placenta and a compensatory reduction in peripheral vascular resistance in the fetal cerebrum, i.e. a brain-sparing effect in the presence of fetal hypoxia [19,20].…”

Regulation of Uterine Spiral Artery Remodeling: a Review

“…However, in most instances, UAR was not examined, experimental interventions used to induce preeclampsia-like symptoms were often applied after the time of placentation, and many of the clinical features of preeclampsia were also induced in nonpregnant rodents, and thus, these models were not specific for pregnancy. Moreover, there are significant differences in placental morphology and development, the process and impact of spiral artery remodeling, uterine and placental vascular anatomy, and the maternal-placenta-fetal endocrine inter-relationships between rodents and humans [ 58 , 59 , 165 – 171 ]. For example, in the mouse and rat, trophoblast invasion is temporally restricted to late gestation [ 58 , 172 ] and the role of UAR on maternal vascular function may be equivocal.…”

The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

“…Implantation and placentation are species-specific processes, and this adds to the difficulty of studying them and their associated pathologies [9]. The depth of trophoblast invasion and spiral artery remodelling mechanism (endovascular route and interstitial route) seems common between great apes (human, chimpanzee, gorilla), but differs from gibbons and baboons, which show shallower endometrial invasion and exclusive use of the endovascular route [10][11][12].…”

“…The TGFβ family has also been shown to play a huge role in placentation, however, with conflicting results (Table 1) [36]. Information on the role of the TGFβ family in nonhuman primates regarding placentation and implantation is limited, but is probably largely conserved with humans [9,10,37]. Signal transduction of the TGFβ family members is initiated by ligand binding to specific transmembrane type I and type II serine/threonine kinase receptors.…”

“…However, those animal models only develop hypertension and not other parameters associated with PE. Hence, although interesting, those are of limited use [9,112].…”